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Gene Review

Smpd1  -  sphingomyelin phosphodiesterase 1, acid...

Mus musculus

Synonyms: A-SMase, ASM, Acid sphingomyelinase, Asm, Sphingomyelin phosphodiesterase, ...
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Disease relevance of Smpd1


High impact information on Smpd1


Chemical compound and disease context of Smpd1


Biological context of Smpd1


Anatomical context of Smpd1

  • Ceramide-independent CD28 and TCR signaling but reduced IL-2 secretion in T cells of acid sphingomyelinase-deficient mice [11].
  • The secreted enzymatic activity was insensitive to digestion with endoglycosidase H but it was stimulated by Zn2+, although to a limited extent compared to aSMase constitutively released by murine endothelial cells [12].
  • Analysis of these animals showed their tissues had no detectable ASM activity, the blood cholesterol levels and sphingomyelin in the liver and brain were elevated, and atrophy of the cerebellum and marked deficiency of Purkinje cells was evident [1].
  • Acidic sphingomyelinase (ASM) is necessary for fas-induced GD3 ganglioside accumulation and efficient apoptosis of lymphoid cells [13].
  • We have analyzed lymphoblastoid cell lines derived from patients affected by Niemann Pick disease (NPD), an autosomal recessive disorder caused by loss-of-function mutations within the acidic sphingomyelinase (ASM) gene [13].

Associations of Smpd1 with chemical compounds

  • Cathepsin D targeted by acid sphingomyelinase-derived ceramide [14].
  • Phorbol esters together with the calcium ionophore A23187 fully reproduced thrombin action on aSMase release [12].
  • Moreover, mannose receptor-mediated transfer of ASM into NPD lymphoblasts rescues their ability to transiently activate ASM, accumulate GD3, and rapidly undergo apoptosis after Fas cross-linking [13].
  • Activation of acid sphingomyelinase and its inhibition by the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway: key events in Escherichia coli-elicited apoptosis of dendritic cells [15].
  • These proapoptotic responses were not only sensitive to inhibitors of sphingomyelinase, PKCzeta, or NADPH oxidases but also to ASM knockdown, bafilomycin, and DIDS, i.e. maneuvers largely preventing hyperosmolarity-induced endosomal acidification and/or ceramide formation [16].

Co-localisations of Smpd1

  • Most A-SMase activity in hairless mice (hr(-/-)) was found in the outer epidermal cell layers and colocalized in the lamellar bodies with A-SMase and sphingomyelin [17].

Regulatory relationships of Smpd1


Other interactions of Smpd1


Analytical, diagnostic and therapeutic context of Smpd1


  1. Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease. Horinouchi, K., Erlich, S., Perl, D.P., Ferlinz, K., Bisgaier, C.L., Sandhoff, K., Desnick, R.J., Stewart, C.L., Schuchman, E.H. Nat. Genet. (1995) [Pubmed]
  2. Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick disease). Otterbach, B., Stoffel, W. Cell (1995) [Pubmed]
  3. PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide. Göggel, R., Winoto-Morbach, S., Vielhaber, G., Imai, Y., Lindner, K., Brade, L., Brade, H., Ehlers, S., Slutsky, A.S., Schütze, S., Gulbins, E., Uhlig, S. Nat. Med. (2004) [Pubmed]
  4. Host acid sphingomyelinase regulates microvascular function not tumor immunity. Garcia-Barros, M., Lacorazza, D., Petrie, H., Haimovitz-Friedman, A., Cardon-Cardo, C., Nimer, S., Fuks, Z., Kolesnick, R. Cancer Res. (2004) [Pubmed]
  5. Acid sphingomyelinase-deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Santana, P., Peña, L.A., Haimovitz-Friedman, A., Martin, S., Green, D., McLoughlin, M., Cordon-Cardo, C., Schuchman, E.H., Fuks, Z., Kolesnick, R. Cell (1996) [Pubmed]
  6. Mannose 6-phosphate receptor-mediated uptake is defective in acid sphingomyelinase-deficient macrophages: implications for Niemann-Pick disease enzyme replacement therapy. Dhami, R., Schuchman, E.H. J. Biol. Chem. (2004) [Pubmed]
  7. Requirement of FADD for tumor necrosis factor-induced activation of acid sphingomyelinase. Wiegmann, K., Schwandner, R., Krut, O., Yeh, W.C., Mak, T.W., Krönke, M. J. Biol. Chem. (1999) [Pubmed]
  8. Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging. Jensen, J.M., Förl, M., Winoto-Morbach, S., Seite, S., Schunck, M., Proksch, E., Schütze, S. Exp. Dermatol. (2005) [Pubmed]
  9. Functional dichotomy of neutral and acidic sphingomyelinases in tumor necrosis factor signaling. Wiegmann, K., Schütze, S., Machleidt, T., Witte, D., Krönke, M. Cell (1994) [Pubmed]
  10. Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages. Liebe, B., Petukhova, G., Barchi, M., Bellani, M., Braselmann, H., Nakano, T., Pandita, T.K., Jasin, M., Fornace, A., Meistrich, M.L., Baarends, W.M., Schimenti, J., de Lange, T., Keeney, S., Camerini-Otero, R.D., Scherthan, H. Exp. Cell Res. (2006) [Pubmed]
  11. Ceramide-independent CD28 and TCR signaling but reduced IL-2 secretion in T cells of acid sphingomyelinase-deficient mice. Stoffel, B., Bauer, P., Nix, M., Deres, K., Stoffel, W. Eur. J. Immunol. (1998) [Pubmed]
  12. Characterization of sphingomyelinase activity released by thrombin-stimulated platelets. Romiti, E., Vasta, V., Meacci, E., Farnararo, M., Linke, T., Ferlinz, K., Sandhoff, K., Bruni, P. Mol. Cell. Biochem. (2000) [Pubmed]
  13. Acidic sphingomyelinase (ASM) is necessary for fas-induced GD3 ganglioside accumulation and efficient apoptosis of lymphoid cells. De Maria, R., Rippo, M.R., Schuchman, E.H., Testi, R. J. Exp. Med. (1998) [Pubmed]
  14. Cathepsin D targeted by acid sphingomyelinase-derived ceramide. Heinrich, M., Wickel, M., Schneider-Brachert, W., Sandberg, C., Gahr, J., Schwandner, R., Weber, T., Saftig, P., Peters, C., Brunner, J., Krönke, M., Schütze, S. EMBO J. (1999) [Pubmed]
  15. Activation of acid sphingomyelinase and its inhibition by the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway: key events in Escherichia coli-elicited apoptosis of dendritic cells. Falcone, S., Perrotta, C., De Palma, C., Pisconti, A., Sciorati, C., Capobianco, A., Rovere-Querini, P., Manfredi, A.A., Clementi, E. J. Immunol. (2004) [Pubmed]
  16. Endosomal acidification and activation of NADPH oxidase isoforms are upstream events in hyperosmolarity-induced hepatocyte apoptosis. Reinehr, R., Becker, S., Braun, J., Eberle, A., Grether-Beck, S., Haüssinger, D. J. Biol. Chem. (2006) [Pubmed]
  17. Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier. Jensen, J.M., Schütze, S., Förl, M., Krönke, M., Proksch, E. J. Clin. Invest. (1999) [Pubmed]
  18. Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation. Egberts, F., Heinrich, M., Jensen, J.M., Winoto-Morbach, S., Pfeiffer, S., Wickel, M., Schunck, M., Steude, J., Saftig, P., Proksch, E., Schütze, S. J. Cell. Sci. (2004) [Pubmed]
  19. Deoxycholic acid activates the c-Jun N-terminal kinase pathway via FAS receptor activation in primary hepatocytes. Role of acidic sphingomyelinase-mediated ceramide generation in FAS receptor activation. Gupta, S., Natarajan, R., Payne, S.G., Studer, E.J., Spiegel, S., Dent, P., Hylemon, P.B. J. Biol. Chem. (2004) [Pubmed]
  20. Stimulation of CD95 (Fas) blocks T lymphocyte calcium channels through sphingomyelinase and sphingolipids. Lepple-Wienhues, A., Belka, C., Laun, T., Jekle, A., Walter, B., Wieland, U., Welz, M., Heil, L., Kun, J., Busch, G., Weller, M., Bamberg, M., Gulbins, E., Lang, F. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  21. Dexamethasone-induced thymocyte apoptosis: apoptotic signal involves the sequential activation of phosphoinositide-specific phospholipase C, acidic sphingomyelinase, and caspases. Cifone, M.G., Migliorati, G., Parroni, R., Marchetti, C., Millimaggi, D., Santoni, A., Riccardi, C. Blood (1999) [Pubmed]
  22. A novel cytoplasmic domain of the p55 tumor necrosis factor receptor initiates the neutral sphingomyelinase pathway. Adam, D., Wiegmann, K., Adam-Klages, S., Ruff, A., Krönke, M. J. Biol. Chem. (1996) [Pubmed]
  23. Tumor necrosis factor alpha activates NF-kappaB in acid sphingomyelinase-deficient mouse embryonic fibroblasts. Zumbansen, M., Stoffel, W. J. Biol. Chem. (1997) [Pubmed]
  24. Role of acidic sphingomyelinase in Fas/CD95-mediated cell death. Lin, T., Genestier, L., Pinkoski, M.J., Castro, A., Nicholas, S., Mogil, R., Paris, F., Fuks, Z., Schuchman, E.H., Kolesnick, R.N., Green, D.R. J. Biol. Chem. (2000) [Pubmed]
  25. Biochemical, pathological, and clinical response to transplantation of normal bone marrow cells into acid sphingomyelinase-deficient mice. Miranda, S.R., Erlich, S., Friedrich, V.L., Haskins, M.E., Gatt, S., Schuchman, E.H. Transplantation (1998) [Pubmed]
  26. Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. Hachem, J.P., Man, M.Q., Crumrine, D., Uchida, Y., Brown, B.E., Rogiers, V., Roseeuw, D., Feingold, K.R., Elias, P.M. J. Invest. Dermatol. (2005) [Pubmed]
  27. Preimplantation diagnosis of a lysosomal storage disorder by in situ enzymatic activity: 'proof of principle' in acid sphingomyelinase-deficient mice. Butler, A., Henderson, S.C., Gordon, R.E., Dagan, A., Gatt, S., Schuchman, E.H. J. Inherit. Metab. Dis. (2005) [Pubmed]
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